Liver disease including hepatitis, liver cirrhosis, and hepatocarcinoma is the most prevalent disease in Korea, Japan, Taiwan, China and other Southeast Asian countries. Presently, liver diseases have been diagnosed by evaluating the content of bilirubin or urobilinogen from patients' urine, by measuring the contents of glutamic-oxaloacetic transaminase (GOT), glutamic pyrubic transaminase, total bilirubin, albumin, lactic acid dehydrogenase and the like so as to analyze the changes of biochemical components in blood and by detecting an antigen from hepatitis B virus (HBV) or hepatitis C virus (HCV) or antibody against these viruses. Besides, liver cirrhosis can be diagnosed by alpha-feto protein (AFP) and carcinoembryonic antigen (CEA) test. However, liver is a complex organ due to various functions and is vitally specific not to reveal an abnormal state outwardly. Furthermore, an early diagnostic method has not been established yet and thus liver disease is often difficult to be treated, since it is diagnosed after severely worsen.
The present inventors have developed a marker which diagnoses a liver disease in a early stage clinically and reflects the severity of patient exactly and then manufactured a diagnostic kit. It has been disclosed in the patent application and the treatise that the marker be a remarkable agent for diagnosing a liver disease.
Precisely, the present inventors have demonstrated the diagnostic method and the diagnostic kit in Korean patent application PCT/KR00/00840 (Aug. 1, 2000), U.S. patent application Ser. No. 09/662,363 (Sep. 13, 2000) and Korean patent application 10-2000-0040609 (Jul. 14, 2000), which exploits the sandwich ELISA method by using the specific antibody and lectin and measures asialo glycoprotein in blood. This techniques are confirmed to be recurrent and accurate and thus to be useful for diagnosing liver functions and to treat hepatic diseases.
It is reported that asialo glycoprotein represent the prognostic status of hepatic disease as a marker in blood serum (T. Sawamura et al., Gastroenterology 1981, 81: 527˜533; T. Sawamura et al., Gastroenterology 1984, 87: 1217˜1221). In addition, it is elucidated that asialo glycoprotein help to detect the status of hepatic cancer since the concentration is proportional to the severity in liver cancer (T. Sawamura et al., Gastrologia Japonica 1985, 20: 201˜208).
Conventionally, the receptor against asialo glycoprotein is separated from human or other animal such as rabbit and mouse, purified and applied as a capture protein in order to measure the concentration of asialo glycoprotein. After it is labeled with radioactive substrates, the competitive radioactive assay and electro immunodiffusion are accomplished (J. S. Marshall et al., J. Lab. Clin. Med. 1978, 92: 30˜37; N. Serbource-Goguel et al., Hepatology 1983, 3: 356˜359).
Unfortunately, there are some problems. Above all, the receptor against asialo glycoprotein is difficult to be obtained in a large scale, although the test kit needs a large amount of asialo glycoprotein. In case of competitive radioreceptor assay, it is dangerous to use radioactive substance and hard to prepare special facilities for treating waste material and the like. In cases of electroimmunodiffusion, it is complicated to analyze data quantitatively. Especially, the competitive assay is not suitable for general diagnostic kit since it lacks accuracy and recurrence.